This research establishes the experimental and theoretical foundation for the development of potentiometric ion sensors with detection limits in the micromolar to picomolar range. The flux of analyte ions from the membrane into the sample which ordinarily perturbs the sample locally at the sensing surface will be minimized by chemical means. Relevant zero-current ion fluxes within plasticized polymeric membranes will be monitored with fluorescence imaging techniques and correlated to appropriate potential drift experiments. Detailed ion flux diffusion models will be developed and correlated to experimental findings. Diffusion coefficients within the membrane phase will be systematically altered with new polyurethane materials with immobilized ionophoric components in view of low detection limit sensing applications. Such polymers will be also used to devise multi-layered membrane phases, which will be applied to generate robust ion gradients within the membrane. Miniature, micrometer sized optical sensor based on the same ionophoric membrane components will be optimized for low detection limit applications and their performance critically compared to their potentiometric counterparts.